Dr. Marcia Brose sits down with Selma Schimmel in The Group Room where she talks about the exciting results presented at ASCO on The DECISION Trial for thyroid cancer patients. They also discuss the nature of targeted therapies vs. standard chemotherapy and the differences in side effects for the patients taking them.

This interview was filmed at the American Society of Clinical Oncology Annual Meeting in Chicago 2013.

Marcia S. Brose, MD, PhD is an Asst. Professor at the Abramson Cancer Center at the University of Pennsylvania.

Advocacy and educational support provided at ASCO 2013, in part, by:

VIDEO TRANSCRIPT

Selma Schimmel, Founder & CEO, Vital Options International:

This is Selma Schimmel and you are looking live at the great city of Chicago which is once again playing host to the American Society of Clinical Oncology: ASCO. This is ASCO’s 49th annual meeting and this year’s theme could not be more appropriate, Building Bridges to Conquer Cancer. More than 30,000 of the world’s foremost cancer specialists are here and so is The Group Room making our 15th appearance at ASCO, and one of our very best. Joining me now is Dr. Marcia Brose: Assistant Professor at the Abramson Cancer Center at the University of Pennsylvania. Welcome, Dr. Brose.

What innovative compounds are available or are showing efficacy now in trials?

Marcia S. Brose, MD, PhD:

So much has happened in the last ten years. We actually now know that over 70% of the patients with the differentiated subtypes of thyroid cancer, actually it’s associated and even medullary too, they’re associated with changes in the kinases that are in the cells. And the kinases that are in the cells are often responsible for the activity of what we call growth or proliferation pathways. Since 2002 we’ve also known that there are BRAF mutations; you may have heard of them because BRAF mutations are in melanoma. So all the sudden at the same time we were finding out molecularly when we underlined new changes in the cells we were also discovering a new class of agents, which are of course kinase inhibitors. They were showing tremendous progress in kidney cancer and advanced liver cancer as far as the drug we were using, which was sorafenib. When you have a rare cancer, while there may be 68,000 thyroid cancers in a year, only maybe 2-6,000 will actually require additional therapy. So now we go from a common cancer down to actually a rare cancer. It’s very hard to get industry to be interested in cancers where not that many people are going to participate- it’s not breast cancer. And so, getting funding and getting the support has also been challenging. We benefit from the bridge from, ‘we had this in renal cancer,’ well there are similarities. Thyroid cancer is very vascular. We’ll take the kinase inhibitors that inhibit angiogenesis, the angiogenesis inhibitors. We’ll take, in thyroid cancer, something that actually maybe has activity with BRAF activity to try to draw parallels with other success stories and that’s exactly what happened here.

At the time we started there were two kinase inhibitors that were readily available, now there are many- it was sorafenib and also sunitinib. At that time, what we did was, we did a phase-II trial and we showed activity. The endocrinologist I worked with, I had to pull her off the roof- she had never, ever seen anyone whose tumor shrunk at all, 5% or 10%, forget the patient that we tried it on. The first patient that we tried it on wasn’t even on a thyroid trial, it was on an addendum to a kidney cancer trial just to see if there was something going on and they had shrinkage of over 30%. This patient did well for actually many years. So, I didn’t know anything about thyroid cancer at that time. I’m a medical oncologist so we don’t even treat it; it wasn’t even on our boards, so we didn’t even know about it. And I was looking at her reaction- I’m like, ‘I think we really need to pursue this.’ I mean, I was going to write the chart and she’s like, ‘absolutely.’ So we actually wrote a phase-II trial, which is a test to see if there is activity. It’s a signal generating trial- it doesn’t give you really the final numbers of how many patients will respond and for how long, but it tells you will there be responses.

Selma Schimmel:

Tell us about the results of the study. And what does this mean going forward?

Marcia S. Brose, MD, PhD:

So the study that we presented here at ASCO is called the DECISION trial and it was the study of sorafenib specifically for patients who failed surgery and radioactive iodine and you have progressing disease. And the exciting news is that when we compared sorafenib to a placebo control group they had a doubling, almost a doubling of their progression-free survival. It was extended from 5.8months in the placebo arm to 10.8months in the treatment arm. And that is just fantastic news. So it really did confirm what we had seen in earlier phase-II studies that sorafenib is clearly active in this group of patients. And then the overall survival information is going to be difficult because there were so many agents available at the time that patients were allowed to cross-over at the time of progression. Both the placebo arm and the sorafenib arm will include patients who ultimately did get sorafenib. So we don’t expect survival to be proven in this study, but I want to point out we didn’t have enough events even to finish the analysis but it does not mean that there’s no survival benefit to this drug. It really… I want to make that very clear, it means that we don’t know and we won’t be able to test that probably from this study; we will have to figure that another way. But, most importantly, that the progression-free survival has been extended and that really is the first time anything has been showing really good efficacy for these patients, and it’s excellent, it’s just amazing.

Selma Schimmel:

The targeted therapies are also very different than the old chemotherapies but when you’re diagnosed and you have to start treatment the first thing a person goes to is chemotherapy.

Marcia S. Brose, MD, PhD:

Correct.

Selma Schimmel:

So let’s talk about how, the good thing that the side-effects associated with these treatments aren’t as debilitating as “classic” or conventional chemotherapy.

Marcia S. Brose, MD, PhD:

That’s very true, and we really have to do a little bit of hand-holding and a lot of education, and remembering that also they don’t come into the oncologist’s office until after they’ve had the disease for a long time. We have some catch up with them often to dispel a lot of fear, misconception, movies that they’ve seen… I mean, their ideas of what it involves, even I would say their ideas of what traditional chemotherapy is probably ten times worse than it really is. But the good news is, the targeted therapies are even better. The side-effects are inconvenient and annoying, but they’re manageable, many times with either creams or over the counter medications. So we really have to let them know that I have many patients who live full lives. They go through the therapy, they’re still working full time, they are doing everything that they were doing. Yes- do they notice that they’re a little bit more tired? Yes- if they’re a triple-A personality maybe they have to scale it back to a double-A. But the bottom line is, the good news is that they are really able to do so much and their life doesn’t stop from the moment that they need therapy.

Selma Schimmel:

You seem like such a warm and really passionate about your area of expertise. Patients are very lucky to have you.

Marcia S. Brose, MD, PhD:

Oh, that’s nice. Thank you.

Selma Schimmel:

There’s a real gentleness about you, like you really must take time to listen to what your patients say.

Marcia S. Brose, MD, PhD:

Well, when you’re treating a rare cancer an interesting thing is there are not many of them, and I will say that they’ve taught me. I wouldn’t be the expert in thyroid cancer if I didn’t have patients who have taught me what it’s like and what matters, because we had to actually address their concerns. And there wasn’t another doctor who was going to teach it to me. It was the patients.

Selma Schimmel:

Dr. Marcia Brose: Assistant Professor at the Abramson Cancer Center at the University of Pennsylvania. Thank you, Dr. Brose.